Sex-Dependent Impacts of Herbicides on the Microbiome

Sex-Dependent Impacts of Round-Up Herbicide on Microbiome It is heavily debated whether the use of the weedkiller glyphosate in agriculture and gardening can induce dysbiosis of the gut microbiota, negatively affecting human and animal health. Dysbiosis is an imbalance in the microbiome composition associated with conditions such as colitis, metabolic syndrome, allergies, and more.

Herbicides and the Microbiome

We recently highlighted new Danish research showing that pure glyphosate and commercial formulations of glyphosate (e.g. Roundup®, Glyfonova®), in doses up to fifty times the European Acceptable Daily Intake value for two weeks, had a close to non-existent impact on the gut microbiota of male rats (n=20). This suggests that glyphosate does not induce microbiota perturbations in healthy adults1.

Glyphosate inhibits the shikimate pathway, a pathway only found in plants and some bacteria, including some of those found in the human gut. The pathway is responsible for the synthesis of essential aromatic amino acids, but since the gut bacteria live in an environment already full of aromatic amino acids coming from the diet, inhibition of the shikimate pathway seems not to be problematic to the bacteria.

As emphasized by the authors, the situation may be different in malnourished individuals, subjects consuming a protein-poor diet or in production animals and further investigations are warranted.

Sex and Microbiome Impacts

However, another recent study indicates that sex could play a role in the severity of microbiome changes from herbicide exposure. In a French study, published in Toxicology Reports shortly after the Danish study, the authors investigated the effect of glyphosate on the gut microbiota of male and female Sprague Dawley® rats over a two-year period2.

Their study reports a dysbiotic effect of Roundup® on the gut microbiota, but only in the female rats. The gut microbiota of treated female rats were characterized by increased levels of the Bacteroidetes family S24-7 and decreased levels of the Lactobacillaceae family, both features previously reported to be associated with dysbiosis.

The treated female rats were significantly different from control females, as well as from control and treated male rats, but the clinical relevance of the observed microbiota alterations remains unresolved. A significant limitation to the French study is that each group consisted of only three rats, an important fact for consideration when interpreting the results.

Implications for Human Health

The potential side effects of glyphosates on the human microbiome is a controversial and heatedly-debated topic. Valid preclinical study design is crucial for providing scientific evidence regarding safety of consumer products to the public and decision-makers.

The French and Danish studies cannot be directly compared, as several factors differ:

  1. Different test compound formulations.
  2. Long-term versus short-term evaluation.
  3. No published information on the baseline microbiome of the animals, which is likely to be different between the two study cohorts.
  4. Bias in how many animals were studied.
However, the results do suggest that sex can influence susceptibility to glyphosate.

It is known that male and female humans and animals can have different microbiome profiles, supposedly due to the different endocrinology of the sexes. Additionally, the host-microbiome cross-talk may happen differently between sexes. Thus, it is sensible to include both males and females in preclinical microbiome studies.

1. Nielsen, L. N. et al. Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels. Environ. Pollut. 233, 364-376 (2018).
2. Lozano, V. L. et al. Sex-dependent impact of Roundup on the rat gut microbiome. Toxicol. Reports 5, 96-107 (2018).

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